2-methoxyimino-2(pyridinyloxymethyl)phenyl acetamides useful as fungicides

ABSTRACT

The present invention provides 2-methoxyimino-2-(pyridinyloxymethyl) phenyl acetamides according to formula (I) as well as their use as fungicidal compounds.

PRIORITY

This application is a 371 of PCT/US 01/29352, which claims priority fromU.S. provisional application serial number 60/233,738, which was filedon Sep. 19, 2000. The entire disclosure of this provisional applicationis hereby incorporated by reference.

FIELD OF THE INVENTION

This invention is related to the field of compounds having fungicidalactivity and processes to make and use such compounds.

BACKGROUND OF THE INVENTION

Our history is riddled with outbreaks of fungal diseases that havecaused widespread human suffering. One need look no further than theIrish potato famine of the 1850's, where an estimated 1,000,000 peopledied, to see the effects of a fungal disease.

Fungicides are compounds, of natural or synthetic origin, which act toprotect plants against damage caused by fungi. Current methods ofagriculture rely heavily on the use of fungicides. In fact, some cropscannot be grown usefully without the use of fungicides. Using fungicidesallows a grower to increase the yield of the crop and consequently,increase the value of the crop. In most situations, the increase invalue of the crop is worth at least three times the cost of the use ofthe fungicide. However, no one fungicide is useful in all situations.

Consequently, research is being conducted to produce fungicides that aresafer, that have better performance, that are easier to use, and thatcost less. In light of the above, the inventors provide this invention.

SUMMARY OF THE INVENTION

It is an object of this invention to provide compounds that havefungicidal activity. It is an object of this invention to provideprocesses that produce compounds that have fungicidal activity. It is anobject of this invention to provide processes that use compounds thathave fungicidal activity. In accordance with this invention, processesto make and processes to use compounds having a general formulaaccording to formula one, and said compounds are provided.

While all the compounds of this invention have fungicidal activity,certain classes of compounds may be preferred for reasons such as, forexample, greater efficacy or ease of synthesis.

DETAILED DESCRIPTION OF THE INVENTION

The compounds have a formula according to formula one. In formula one:

A is selected from the group consisting of oxy (—O—) and amino (—NH—);

E is selected from the group consisting of aza (—N═) and methine (—CH═);

j¹, j², j³, and J⁴ are independently selected from the group consistingof hydro (—H), halo (—F, —Cl, —Br, and —I), C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₄alkyl (mono or multi-halo), and C₁₋₄ alkylthio;

M¹, M², and M³ are selected from the group consisting of hydro (—H),halo (—F, —Cl, —Br, and —I), C₁₋₄ alkyl, Cl₄ alkoxy, C₁₋₄ alkyl (mono ormulti-halo), and C₁₋₄ alkylthio, nitro (—NO₂), (mono or multi-halo) C₁₋₄alkoxy;

Q is selected from the group consisting of oxy (—O—), NX (where X isselected from the group consisting of hydro (—H) and C₁₋₄ alkyl, or X isthe connecting bond to the pyridyl), and CZ¹ Z² (where each Z isindependently selected from the group consisting of hydro (—H) and C₁₋₄alkyl, or one Z is the connecting bond to the pyridyl);

R is selected from the group consisting of oxy (—O—), NX¹ (where X₁ isselected from the group consisting of hydro (—H) and C₁₋₄ alkyl, or X¹is the connecting bond to the pyridyl), and CZ³ Z⁴ (where each Z isindependently selected from the group consisting of hydro (—H) and C₁₋₄alkyl, or one Z is the connecting bond to the pyridyl); and

T is a C₁₋₂ carbon atom chain connecting Q to R where each carbon atomin this chain is fully saturated. Consequently, each carbon atom in thechain in T has four other single bonds. T can be optionally substitutedwith a C₁₋₄ alkyl or one of the single bonds can be the connecting bondto the pyridyl.

The term “alkyl”, “alkenyl”, or “alkynyl” refers to an unbranched orbranched chain carbon group. The term “alkoxy” refers to an unbranchedor branched chain alkoxy group. The term “haloalkyl” refers to anunbranched or branched alkyl group substituted with one or more haloatoms. The term “haloalkoxy” refers to an alkoxy group substituted withone or more halo atoms. Throughout this document, all temperatures aregiven in degrees Celsius and all percentages are weight percentages,unless otherwise stated. The term “Me” refers to a methyl group. Theterm “Et” refers to an ethyl group. The term “Pr” refers to a propylgroup. The term “Bu” refers to a butyl group. The term “EtOAc” refers toethyl acetate. The term “ppm” refers to parts per million. The term,“psi” refers to pounds per square inch.

In general, these compounds can be used in a variety of ways. Thesecompounds are preferably applied in the form of a formulation comprisingone or more of the compounds with a phytologically acceptable carrier.Concentrated formulations can be dispersed in water, or another liquid,for application, or formulations can be dust-like or granular, which canthen be applied without further treatment. The formulations are preparedaccording to procedures which are conventional in the agriculturalchemical art, but which are novel and important because of the presencetherein of one or more of the compounds.

The formulations that are applied most often are aqueous suspensions oremulsions. Either such water-soluble, water suspendable, or emulsifiableformulations are solids, usually known as wettable powders, or liquids,usually known as emulsifiable concentrates, aqueous suspensions, orsuspension concentrates. The present invention contemplates all vehiclesby which one or more of the compounds can be formulated for delivery anduse as a fungicide.

As will be readily appreciated, any material to which these compoundscan be added may be used, provided they yield the desired utilitywithout significant interference with the activity of these compounds asantifungal agents.

Wettable powders, which may be compacted to form water dispersiblegranules, comprise an intimate mixture of one or more of the compounds,an inert carrier and surfactants. The concentration of the compound inthe wettable powder is usually from about 10% to about 90% w/w, morepreferably about 25% to about 75% w/w. In the preparation of wettablepowder formulations, the compounds can be compounded with any of thefinely divided solids, such as prophyllite, talc, chalk, gypsum,Fuller's earth, bentonite, attapulgite, starch, casein, gluten,montmorillonite clays, diatomaceous earths, purified silicates or thelike. In such operations, the finely divided carrier is ground or mixedwith the compounds in a volatile organic solvent. Effective surfactants,comprising from about 0.5% to about 10% of the wettable powder, includesulfonated lignins, naphthalenesulfonates, alkylbenzenesulfonates, alkylsulfates, and non-ionic surfactants, such as ethylene oxide adducts ofalkyl phenols.

Emulsifiable concentrates of the compounds comprise a convenientconcentration, such as from about 10% to about 50% w/w, in a suitableliquid. The compounds are dissolved in an inert carrier, which is eithera water miscible solvent or a mixture of water-immiscible organicsolvents, and emulsifiers. The concentrates may be diluted with waterand oil to form spray mixtures in the form of oil-in-water emulsions.Usefully organic solvents include aromatics, especially the high-boilingnaphthalenic and olefinic portions of petroleum such as heavy aromaticnaphtha. Other organic solvents may also be used, such as, for example,terpenic solvents, including rosin derivatives, aliphatic ketones, suchas cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.

Emulsifiers which can be advantageously employed herein can be readilydetermined by those skilled in the art and include various nonionic,anionic, cationic and amphoteric emulsifiers, or a blend of two or moreemulsifiers. Examples of nonionic emulsifiers useful in preparing theemulsifiable concentrates include the polyalkylene glycol ethers andcondensation products of alkyl and aryl phenols, aliphatic alcohols,aliphatic amines or fatty acids with ethylene oxide, propylene oxidessuch as the ethoxylated alkyl phenols and carboxylic esters solubilizedwith the polyol or polyoxyalkylene. Cationic emulsifiers includequaternary ammonium compounds and fatty amine salts. Anionic emulsifiersinclude the oil-soluble salts (e.g., calcium) of alkylaryl sulphonicacids, oil soluble salts or sulphated polyglycol ethers and appropriatesalts of phosphated polyglycol ether.

Representative organic liquids which can be employed in preparing theemulsifiable concentrates of the present invention are the aromaticliquids such as xylene, propyl benzene fractions; or mixed naphthalenefractions, mineral oils, substituted aromatic organic liquids such asdioctyl phthalate; kerosene; dialkyl amides of various fatty acids,particularly the dimethyl amides of fatty glycols and glycol derivativessuch as the n-butyl ether, ethyl ether or methyl ether of diethyleneglycol, and the methyl ether of triethylene glycol. Mixtures of two ormore organic liquids are also often suitably employed in the preparationof the emulsifiable concentrate. The preferred organic liquids arexylene, and propyl benzene fractions, with xylene being most preferred.The surface-active dispersing agents are usually employed in liquidformulations and in the amount of from 0.1 to 20 percent by weight ofthe combined weight of the dispersing agent with one or more of thecompounds. The formulations can also contain other compatible additives,for example, plant growth regulators and other biologically activecompounds used in agriculture.

Aqueous suspensions comprise suspensions of one or more water-insolublecompounds, dispersed in an aqueous vehicle at a concentration in therange from about 5% to about 50% w/w. Suspensions are prepared by finelygrinding one or more of the compounds, and vigorously mixing the groundmaterial into a vehicle comprised of water and surfactants chosen fromthe same types discussed above. Other ingredients, such as inorganicsalts and synthetic or natural gums, may also be added to increase thedensity and viscosity of the aqueous vehicle. It is often most effectiveto grind and mix at the same time by preparing the aqueous mixture andhomogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer.

The compounds may also be applied as granular formulations, which areparticularly useful for applications to the soil. Granular formulationsusually contain from about 0.5% to about 10% w/w of the compounds,dispersed in an inert carrier which consists entirely or in large partof coarsely divided attapulgite, bentonite, diatomite, clay or a similarinexpensive substance. Such formulations are usually prepared bydissolving the compounds in a suitable solvent and applying it to agranular carrier which has been preformed to the appropriate particlesize, in the range of from about 0.5 to about 3 mm. Such formulationsmay also be prepared by making a dough or paste of the carrier and thecompound, and crushing and drying to obtain the desired granularparticle.

Dusts containing the compounds are prepared simply by intimately mixingone or more of the compounds in powdered form with a suitable dustyagricultural carrier, such as, for example, kaolin clay, ground volcanicrock, and the like. Dusts can suitably contain from about 1% to about10% w/w of the compounds.

The formulations may contain adjuvant surfactants to enhance deposition,wetting and penetration of the compounds onto the target crop andorganism. These adjuvant surfactants may optionally be employed as acomponent of the formulation or as a tank mix. The amount of adjuvantsurfactant will vary from 0.01 percent to 1.0 percent v/v based on aspray-volume of water, preferably 0.05 to 0.5%. Suitable adjuvantsurfactants include ethoxylated nonyl phenols, ethoxylated synthetic ornatural alcohols, salts of the esters or sulphosuccinic acids,ethoxylated organosilicones, ethoxylated fatty amines and blends ofsurfactants with mineral or vegetable oils.

The formulations may optionally include combinations that can compriseat least 1% of one or more of the compounds with another pesticidalcompound. Such additional pesticidal compounds may be fungicides,insecticides, nematocides, miticides, arthropodicides, bactericides orcombinations thereof that are compatible with the compounds of thepresent invention in the medium selected for application, and notantagonistic to the activity of the present compounds. Accordingly, insuch embodiments the other pesticidal compound is employed as asupplemental toxicant for the same or for a different pesticidal use.The compounds and the pesticidal compound in the combination cangenerally be present in a weight ratio of from 1:100 to 100:1

The present invention includes within its scope methods for the controlor prevention of fungal attack. These methods comprise applying to thelocus of the fungus, or to a locus in which the infestation is to beprevented (for example applying to cereal or grape plants), a fungicidalamount of one or more of the compounds. The compounds are suitable fortreatment of various plants at fungicidal levels, while exhibiting lowphytotoxicity. The compounds are useful in a protectant or eradicantfashion. The compounds are applied by any of a variety of knowntechniques, either as the compounds or as formulations comprising thecompounds. For example, the compounds may be applied to the roots, seedsor foliage of plants for the control of various fungi, without damagingthe commercial value of the plants. The materials are applied in theform of any of the generally used formulation types, for example, assolutions, dusts, wettable powders, flowable concentrates, oremulsifiable concentrates. These materials are conveniently applied invarious known fashions.

The compounds have been found to have significant fungicidal effectparticularly for agricultural use. Many of the compounds areparticularly effective for use with agricultural crops and horticulturalplants, or with wood, paint, leather or carpet backing.

In particular, the compounds effectively control a variety ofundesirable fungi that infect useful plant crops. Activity has beendemonstrated for a variety of fungi, including for example the followingrepresentative fungi species:

Downy Mildew of Grape (Plasmopara viticola—PLASVI);

Late Blight of Tomato (Phytophthora infestans—PHYTIN);

Apple Scab (Venturia inaequalis—VENTIN);

Brown Rust of Wheat (Puccinia recondita—PUCCRT);

Stripe Rust of Wheat (Puccinia striiformis—PUCCST);

Rice Blast (Pyricularia oryzae—PYRIOR);

Cercospora Leaf Spot of Beet (Cercospora beticola—CERCBE);

Powdery Mildew of Wheat (Erysiphe graminis—ERYSGT);

Leaf Blotch of Wheat (Septoria tritici—SEPTTR);

Sheath Blight of Rice (Rhizoctonia solani—RHIZSO);

Eyespot of Wheat (Pseudocercosporella herpotrichoides—PSDCHE);

Brown Rot of Peach (Monilinia fructicola—MONIFC); and

Glume Blotch of Wheat (Septoria nodorum—LEPTNO).

It will be understood by those in the art that the efficacy of thecompound for the foregoing fungi establishes the general utility of thecompounds as fungicides.

The compounds have broad ranges of efficacy as fungicides. The exactamount of the active material to be applied is dependent not only on thespecific active material being applied, but also on the particularaction desired, the fungal species to be controlled, and the stage ofgrowth thereof, as well as the part of the plant or other product to becontacted with the compound. Thus, all the compounds, and formulationscontaining the same, may not be equally effective at similarconcentrations or against the same fungal species.

The compounds are effective in use with plants in a disease inhibitingand phytologically acceptable amount. The term “disease inhibiting andphytologically acceptable amount” refers to an amount of a compound thatkills or inhibits the plant disease for which control is desired, but isnot significantly toxic to the plant. This amount will generally be fromabout 1 to about 1000 ppm, with 10 to 500 ppm being preferred. The exactconcentration of compound required varies with the fungal disease to becontrolled, the type of formulation employed, the method of application,the particular plant species, climate conditions, and the like. Asuitable application rate is typically in the range from about 0.10 toabout 4 pounds/acre.

EXAMPLES

These examples are provided to further illustrate the invention. Theyare not meant to be construed as limiting the invention.

A mixture of 5,6-dichloro-pyridine-3-aldehyde (3.0 g, 0.017 mol),anhydrous sodium acetate (3.0 g, 0.037 mol), hydroxylamine hydrochloride(2.0 g, 0.029 mol) and ethanol (50 mL) was heated with stirring underreflux conditions for 3 hours. The mixture was cooled to roomtemperature, poured into water (250 mL) and filtered. The resultingwhite solid was dissolved in dichloromethane (200 mL), and the solutiondried over anhydrous sodium sulphate. Evaporation of the solvent underreduced pressure and recrystallization of the residue from ethyl acetategave the desired product (2.90 g, 89%) as a white solid, melting point.150-2° C.

5,6-Dichloro-pyridine-3-aldehyde, oxime (0.96 g, 5 mmol) was dissolvedwith stirring in a 0.5M solution of hydrogen chloride in DMF (11 mL),and OXONE□ (1.69 g, 2.75 mmol) added. The mixture was stirred for 5hours, additional OXONE (0.85 g, 1.38 mmol) added, and the mixturestirred overnight. It was poured into ice water, and the resultant solidcollected by filtration and dried. Recrystallization from ethyl acetate:hexane gave the desired product (0.97 g, 86%) as a white solid, meltingpoint. 185-6° C.

5,6-Dichloro-N-hydroxy-3-pyridinecarboximidoyl chloride (1.0 g, 4.5mmol) was dissolved with stirring in ether (50 mL) and a solution oftriethylamine (1.0 g, 10 mmol) in ether (50 mL) added dropwise to thesolution while isobutylene was bubbled through the reaction mixture. Themixture was stirred at room temperature overnight, filtered, and thefiltrate evaporated to dryness under reduced pressure. Recrystallizationof the residue from hexane gave the desired product (0.73 g, 66%) as acream solid, melting point. 91-3° C.

3-(2,3-Dichloro-5-pyridyl)-5,5-dimethyl-4, 5-dihydroisoxazole (0.60 g,2.4 mmol) was dissolved in t-butanol (25 mL) and sodium methanethiolate(0.21 g, 3.0 mmol) added. The reaction mixture was heated at 45° C. withstirring for 3 hours, cooled, and poured onto ice. The resulting creamprecipitate was collected by filtration, dissolved in dichloromethane(50 mL), and dried over anhydrous sodium sulphate. Evaporation of thesolvent under reduced pressure gave the desired product (0.50 g, 81%) asa cream solid.

3-(3-Chloro-2-methylthio-5-pyridyl)-5,5-dimethyl4, 5-dihydroisoxazole(0.56 g, 2.2 mmol) was dissolved with stirring in dichloromethane (50mL) and m-chloroperoxybenzoic acid (1.40 g, 60% assay, 4.9 mmol) added.The mixture was stirred at room temperature for 4 hours and 10% sodiumcarbonate solution (50 mL) added. The mixture was separated and theorganic phase washed three times with 2M sodium hydroxide solution(50mL) and brine. It was dried over anhydrous sodium sulphate andevaporated under reduced pressure to give the desired product as a clearoil that solidifies on standing (0.58 g, 90%).

2-(Hydroxymethyl)-a-(methoxyimino)-N-methylbenzeneacetamide (0.42 g, 1.9mmol) was dissolved with stirring in anhydrous THF (20 mL) and 60%sodium hydride (0.14 g, 3.46 mmol) added. The mixture was stirred atroom temperature for 30 minutes and a solution of3-(3-chloro-2-methylsulphonyl-5-pyridyl)-5,5-dimethyl4,5-dihydroisoxazole (0.5 g, 1.74 mmol) in anhydrous THF (15 mL) added.The resultant mixture was heated at 50° C. with stirring for 4 hours,cooled, and poured into water. It was then extracted twice with ethylacetate (50 mL), the organic extracts combined, and washed with water(50 mL) and brine (50 mL). It was dried over anhydrous sodium sulphate,evaporated to dryness under reduced pressure, and the residue purifiedby chromatography over silica (5-40% ethyl acetate: hexane) to give thedesired product (0.55 g, 68%) as a clear oil, which solidifies onstanding.

A mixture of 2-amino-2-methyl-propan-1-ol (2.11 g, 0.024 mol) andtriethylamine (4.8 g, 0.048 mol) in dichloromethane (50 mL) was stirredand cooled to 0° C. A solution of 5,6-dichloronicotinoyl chloride (2.5g, 0.012 mol) in dichloromethane (25 mL) was added dropwise and themixture stirred overnight. Water (25 mL) was added and the mixtureseparated. The organic phase was washed with 10% sodium carbonatesolution (50 mL), water (25 mL), 2M hydrochloric acid (50 mL), and brine(50 mL). It was then dried over anhydrous sodium sulphate and evaporatedunder reduced pressure to give the desired compound (2.72 g, 86%) as apale orange oil.

N-(2-Hydroxy-1, 1, -dimethylethyl)-5,6-dichloropyridine-5-carboxamide(0.50 g, 1.90 mmol) was dissolved with stirring in dichloromethane (20mL) and cooled to −78° C. Diethylaminosulphur trifluoride (0.34 g, 2.12mmol) was added dropwise and the mixture stirred at −78° C. for onehour. The mixture was quenched at low temperature with 4M ammoniumhydroxide solution (20 mL) and warmed to room temperature. The mixturewas separated and the solvent evaporated under reduced pressure to givea tan oil. Purification of this oil by reverse phase HPLC (70:30acetonitrile: water) gave the desired product (0.44 g, 94%) as a clearoil which crystallizes on standing.

2-(5,6-Dichloro-3-pyridyl)-5,5-dimethyl4, 5-dihydrooxazole (2.0 g, 8.2mmol) was dissolved with stirring in t-butanol (40 mL) and sodiummethanethiolate (0.69 g, 9.80 mmol) added. The mixture was stirred at60° C. for six hours, cooled to room temperature, and poured into water.The mixture was extracted with dichloromethane (50 mL) and the organicphase washed with water (50 mL) and brine (50 mL), and dried overanhydrous sodium sulphate. Evaporation of the solvent under reducedpressure gave the desired product as a cream solid (1.3 g, 62%), m. pt.113-5° C.

2-(5-Chloro-6-methylthio-3-pyridyl)-5,5-dimethyl-4, 5-dihydrooxazole(1.0g, 3.7 mmol) was dissolved with stirring in dichloromethane (50 mL)and m-chloroperoxybenzoic acid (2.36 g, 60% assay, 8.2 mmol) added. Themixture was stirred overnight, 10% sodium carbonate solution (50 mL)added, and the mixture stirred for one hour. This was separated and theorganic phase washed twice with 2M sodium hydroxide solution (30 mL) andwith brine (25 mL). Drying over anhydrous sodium sulphate andevaporation of the solvent under reduced pressure gave the desiredproduct (0.9 g, 80%) as a white solid, m. pt 102-5° C.

2-(Hydroxymethyl)-α-(methoxyimino)-N-methylbenzeneacetamide (0.32 g,1.45 mmol) was dissolved with stirring in anhydrous THF (20 mL) and 60%sodium hydride (0.12 g, 3.0 mmol) added. The mixture was stirred at roomtemperature for 30 minutes and a solution of2-(5-chloro-6-methylsulphonyl-3-pyridyl)-5,5-dimethyl-4,5-dihydrooxazole (0.4 g, 1.39 mmol) in anhydrous THF (15 mL) added. Theresultant mixture was heated at 50° C. with stirring for 4 hours,cooled, and poured into water. It was then extracted twice with ethylacetate (50 mL), the organic extracts combined, and washed with water(50 mL) and brine (50 mL). It was dried over anhydrous sodium sulphate,evaporated to dryness under reduced pressure, and the residue purifiedby chromatography over silica (10-50% ethyl acetate: hexane) to give thedesired product (0.35 g, 58%) as a white solid, melting point. 145-7° C.

A mixture of 3-amino-3-methyl-butan-1-ol (0.98 g, 9.45 mmol) and aqueous1N sodium hydroxide (30 ml) in dichloromethane (20 mL) was stirred. Asolution of 5,6-dichloronicotinoyl chloride (2.0 g, 9.45 mmol) indichloromethane (20 mL) was added dropwise and the mixture stirredovernight. The mixture was neutralized with 1N HCl and it was pouredinto water. It was then extracted three times with dichloromethane (25mL). The organic extracts were combined and washed twice with water (50mL) and once with brine (50 mL). It was dried over anhydrous sodiumsulphate, filtered, and evaporated to dryness under reduced pressure togive the desired compound (1.08 g, 41%) as a yellow sticky solid.

N-(3-Hydroxy-1, 1, -dimethylethyl)-5,6-dichloropyridine-5-carboxamide(0.50 g, 1.80 mmol) was dissolved with stirring in dichloromethane (20mL) and cooled to −78° C. Diethylaminosulphur trifluoride (0.26 ml, 1.98mmol) was added dropwise and the mixture stirred at −78° C. for onehour. The mixture was quenched at low temperature with 4M ammoniumhydroxide solution (10 mL), warmed to room temperature, and stirredovernight. The mixture was poured into water (25 ml) and extracted freetimes with dichloromethane (25 ml). The organic extracts were combinedand washed once with water (50 ml) and once with brine (50 ml). It wasdried over sodium sulfate, filtered, and evaporated under reducedpressure to dryness. The residue was purified by chromatography oversilica (25-50% ethyl acetate: hexane) to give the desired product as ayellow crystalline solid (0.27 g, 59%).

2-(Hydroxymethyl)-□-(methoxyimino)-N-methylbenzeneacetamide (0.14 g,0.637 mmol) was dissolved with stirring in anhydrous THF (25 mL) and 60%sodium hydride (32 mg, 0.810 mmol) added. The mixture was stirred atroom temperature for 15 minutes and2-(5,6-dichloro-3-pyridyl)4,4-dimethyl-5, 6-dihydrooxazine (0.15 g,0.579 mmol) was added. The resultant mixture was heated at 50° C. withstirring for 3 hours, cooled, and stirred at room temperature overnight.Anhydrous dimethylsulfoxide (1 ml) was added and the mixture wasreheated to 50° C. with stirring for 3 hours and cooled to roomtemperature. The mixture was quenched with water (15 ml) and extractedthree times with ethyl acetate (25 mL). The organic extracts werecombined, washed twice with water (25 mL), and once with brine (30 mL).It was dried over anhydrous sodium sulphate, filtered, and evaporated todryness under reduced pressure. The residue purified by chromatographyover silica (20-50% ethyl acetate: hexane) to give the desired product(35 mg, 14%) as a clear oil.

A mixture of 2-amino-butan-1-ol (2.11 g, 0.024 mol) and triethylamine(4.8 g, 0.048 mol) in dichloromethane (50 mL) was stirred and cooled to0° C. A solution of 5,6-dichloronicotinoyl chloride (2.5 g, 0.012 mol)in dichloromethane (25 mL) was added dropwise and the mixture stirredovernight. Water (25 mL) was added and the mixture separated. Theorganic phase was washed with 10% sodium carbonate solution (50 mL),water (25 mL), 2M hydrochloric acid (50 mL) and brine (50 mL). It wasthen dried over anhydrous sodium sulphate and evaporated under reducedpressure to give the desired compound (1.99 g, 63%) as a tan solid,melting point 107-9° C.

N-(4-hydroxy-2-butyl)-5,6-dichloropyridine-5-carboxamide (0.50 g, 1.90mmol) was dissolved with stirring in dichloromethane (20 mL) and cooledto −78° C. Diethylaminosulphur trifluoride (0.34 g, 2.12 mmol) was addeddropwise and the mixture stirred at −78° C. for one hour. The mixturewas quenched at low temperature with 4M ammonium hydroxide solution (20mL) and warmed to room temperature. The mixture was separated and thesolvent evaporated under reduced pressure to give a tan oil.Purification by chromatography over silica (0-10% ethyl acetate:pentane) gave the desired product (0.42 g, 90%) as a clear oil.

2-(Hydroxymethyl)-α-(methoxyimino)-N-methylbenzeneacetamide (0.32 g,1.45 mmol) was dissolved with stirring in anhydrous THF (20 mL) and 60%sodium hydride (0.12 g, 3.0 mmol) added. The mixture was stirred at roomtemperature for 30 minutes and a solution of2-(5,6-dichloro-3-pyridyl)-5-ethyl-4,5-dihydrooxazole (0.4 g, 1.39n-mol)in anhydrous THF (15 mL) added. The resultant mixture was heated at 50°C. with stirring for 4 hours, cooled, and poured into water. It was thenextracted twice with ethyl acetate (50 nL), the organic extractscombined, and washed with water (50 mL) and brine (50 mL). It was driedover anhydrous sodium sulphate, evaporated to dryness under reducedpressure, and the residue purified by chromatography over silica (10-50%ethyl acetate: hexane) to give the desired product (0.42 g, 70%) as aclear oil.

A mixture of 2-hydroxybutylamine (2.11 g, 0.024 mol) and triethylamine(4.8 g, 0.048 mol) in dichloromethane (50 mL) was stirred and cooled to0° C. A solution of 5,6-dichloronicotinoyl chloride (2.5 g, 0.012 mol)in dichloromethane (25 mL) was added dropwise and the mixture stirredovernight. Water (25 mL) was added and the mixture separated. Theorganic phase was washed with 10% sodium carbonate solution (50 mL),water (25 mL), 2M hydrochloric acid (50 mL) and brine (50 mL). It wasthen dried over anhydrous sodium sulphate and evaporated under reducedpressure to give the desired compound (2.70 g, 85%) as a white solid,melting point 128-31° C.

N-(2-Hydroxybutyl)-5,6-dichloropyridine-5-carboxamide (0.50 g, 1.90mmol) was dissolved with stirring in dichloromethane (20 mL) and cooledto −78° C. Diethylaminosulphur trifluoride (0.34 g, 2.12 mmol) was addeddropwise and the mixture stirred at −78° C. for one hour. The mixturewas quenched at low temperature with 4M ammonium hydroxide solution (20mL) and warmed to room temperature. The mixture was separated and thesolvent evaporated under reduced pressure to give a tan oil.Purification of this oil by chromatography over silica (5-30% ethylacetate: hexane) gave the desired product (0.45 g, 96%) as a clear oil.

2-(5,6-Dichloro-3-pyridyl)4ethyl-4,5-dihydrooxazole (2.0 g, 8.2 mmol)was dissolved with stirring in t-butanol (40 mL) and sodiummethanethiolate (0.69 g, 9.80 mmol) added. The mixture was stirred at60° C. for six hours, cooled to room temperature, and poured into water.The mixture was extracted with dichloromethane (50 mL) and the organicphase washed with water (50 mL) and brine (50 mL), and dried overanhydrous sodium sulphate. Evaporation of the solvent under reducedpressure gave the desired product as a yellow oil (2.4 g, 91%).

2-(5-Chloro-6-methylthio-3-pyridyl)4ethyl-4,5-dihydrooxazole (1.0 g, 3.7mmol) was dissolved with stirring in dichloromethane (50 mL) andm-chloroperoxybenzoic acid (2.36 g, 60% assay, 8.2 mmol) added. Themixture was stirred overnight, 10% sodium carbonate solution (50 mL)added, and the mixture stirred for one hour. This was separated and theorganic phase washed twice with 2M sodium hydroxide solution (30 mL) andwith brine (25 mL). Drying over anhydrous sodium sulphate andevaporation of the solvent under reduced pressure gave the desiredproduct (0.9 g, 80%) as a clear oil which solidifies on standing.

2-(Hydroxymethyl)-α-(methoxyimino)-N-methylbenzeneacetamide (0.32 g,1.45 mmol) was dissolved with stirring in anhydrous THF (20 mL) and 60%sodium hydride (0.12 g, 3.0 mmol) added. The mixture was stirred at roomtemperature for 30 minutes and a solution of2-(5-chloro-6-methylsulphonyl-3-pyridyl)4-10 ethyl-4,5-dihydrooxazole(0.4 g, 1.39 mmol) in anhydrous THF (15 mL) added. The resultant mixturewas heated at 50° C. with stirring for 4 hours, cooled, and poured intowater. It was then extracted twice with ethyl acetate (50 mL), theorganic extracts combined, and washed with water (50 mL) and brine (50mL). It was dried over anhydrous sodium sulphate, evaporated to drynessunder reduced pressure, and the residue purified by chromatography oversilica (10-50% ethyl acetate: hexane) to give the desired product (0.42g, 70%) as an oily solid.

A mixture of(2E)-2-[2-(hydroxymethyl)phenyl]-2-(methoxyimino)-N-methylethanamide (80mg, 0.36 mmol) and sodium hydride (60% suspension in mineral oil; 15 mg,0.37 mmol) in anhydrous tetrahydrofuran (2 mL) under nitrogen wasstirred for 2 minutes at ambient temperature, then a solution of5-(4,5-dihydroisoxazol-3-yl)-2-fluoro-3-methylpyridine (60 mg, 0.33mmol) in anhydrous tetrahydrofuran (3 mL) was added, and the mixture wasstirred for 18 hours. TLC analysis showed one major new component(R_(f)=0.44, CH₂Cl₂-EtOAc 2:1). The mixture was partitioned betweenether (30 mL) and saturated aqueous NH₄Cl (10 mL), and the organic phasewas washed with water and brine, dried (MgSO₄), filtered andconcentrated under vacuum. Chromatography of the residue on apreparative plate of silica gel (20×20 cm, 2 mm thickness), eluting withCH₂Cl₂-EtOAc 2:1, afforded 78 mg (63%) of the desired title compound asa white solid. Spectral data were consistent with the assignedstructure.

BIOLOGICAL RESULTS

The compounds were formulated at 100 ppm in 10% acetone plus 0.01%Triton X100 and tested for efficacy at the whole plant level in a 1-dayprotectant test (1DP). Chemicals were sprayed on a turn table sprayerfitted with two opposing air atomization nozzles which deliveredapproximately 1500 L/ha of spray volume. Disease severity was evaluated1 to 3 weeks later.

Compound Formulation: Compound formulation was accomplished bydissolving technical materials in acetone, with serial dilutions thenmade in acetone to obtain desired rates. Final treatment volumes wereobtained by adding nine volumes 0.05% aqueous Tween-20 or Triton X-100,depending upon the pathogen.

Late Blight of Tomatoes (Phytophthora infestans—PHYTMN): Tomatoes(cultivar Rutgers) were grown from seed in a soilless peat-based pottingmixture (Metromix) until the seedlings were 1-2 leaf (BBCH 12). Theseplants were then sprayed to run off with the test compound at a rate of100 ppm. After 24 hours the test plants were inoculated with an aqueousspore suspension of Phytophthora infestans. The plants were thentransferred to the greenhouse until disease developed on the untreatedcontrol plants.

Powdery Mildew of Wheat (Erysiphe graminis—ERYSGT): Wheat (cultivarMonon) was grown in a soilless peat-based potting mixture (Metromix)until the seedlings were 1-2 leaf (BBCH 12). These plants were thensprayed to run off with the test compound at a rate of 100 ppm. After 24hours the test plants were inoculated with Erysiphe graminis by dustingspores from stock plants onto the test plants. The plants were thentransferred to the greenhouse until disease developed on the untreatedcontrol plants.

Glume blotch of wheat (Leptosphaeria nodorum—LEPTNO): Wheat (cultivarMonon) was grown from seed in a soilless peat-based potting mixture(Metromix) until the seedlings were 1-2 leaf (BBCH 12). These plantswere then sprayed to run off with the test compound at a rate of 100ppm. After 24 hours the test plants were inoculated with an aqueousspore suspension of Leptosphaeria nodorum. The plants were thentransferred to the greenhouse until disease developed on the untreatedcontrol plants.

Brown rust (Puccinia recondita—PUCCRT): Wheat (cultivar Monon) was grownfrom seed in a soilless peat-based potting mixture (Metromix) until theseedlings were 1-2 leaf (BBCH 12). These plants were then sprayed to runoff with the test compound at a rate of 100 ppm. After 24 hours the testplants were inoculated with an aqueous spore suspension of Pucciniarecondita. The plants were then transferred to the greenhouse untildisease developed on the untreated control plants.

The following table presents the activity of typical compounds of thepresent invention when evaluated in these experiments. The effectivenessof the test compounds in controlling disease was rated by giving thepercent control of the plant disease.

TABLE ONE “BIOLOGICAL DATA FOR COMPOUNDS 1-6”

Compound ERYSGT LEPTNO PHYTIN PUCCRT Number R Het 1DP 1DP 1DP 1DP 1 Me

>95 ? >95 >95 2 Cl

>95 >80 <50 >95 3 Cl

>95 <50 <50 >95 4 Cl

>80 >95 <50 >95 5 Cl

>80 >95 <50 >95 6 Cl

>80 >95 <50 >95 ? = Not tested

?=Not tested

What is claimed is:
 1. A compound according to formula one

wherein A is selected from the group consisting of oxy (—O—) and amino(—NH—); E is selected from the group consisting of aza (—N═) and methine(—CH═); j¹, j², j³, and j⁴ are independently selected from the groupconsisting of hydro (—H), halo (—F, —Cl, —Br, and —I), C₁₋₄ alkyl, C₁₋₄alkoxy, C₁₋₄ alkyl (mono or multi-halo), and C₁₋₄ alkylthio; M¹, M², andM³ are selected from the group consisting of hydro (—H), halo (—F, —Cl,—Br, and —I), C₁₋₄ alkyl, C₁₋₄ alloxy, C₁₋₄ alkyl (mono or multi-halo),and C₁₋₄ alkylthio, nitro (—NO₂), (mono or multi-halo) C₁₋₄ alkoxy; Q isselected from the group consisting of oxy (—O—), NX (where X is selectedfrom the group consisting of hydro (—H) and C₁₋₄ alkyl, or X is theconnecting bond to the pyridyl), and CZ¹ Z² (where each Z isindependently selected from the group consisting of hydro (—H) and C₁₋₄alkyl, or one Z is the connecting bond to the pyridyl); R is selectedfrom the group consisting of oxy (—O—), NX¹ (where X¹ is selected fromthe group consisting of hydro (—H) and C₁₋₄ alkyl, or X¹ is theconnecting bond to the pyridyl), and CZ³ Z⁴ (where each Z isindependently selected from the group consisting of hydro (—H) and C₁₋₄alkyl, or one Z is the connecting bond to the pyridyl); and T is a C₁₋₂carbon atom chain connecting Q to R where each carbon atom in this chainis fully saturated.
 2. A compound according to claim 1 wherein A isamino (—NH—).
 3. A compound according to claim 1 wherein E is aza (—N═).4. A compound according to claim 1 wherein J¹, J², J³,and J⁴ are hydro(—H).
 5. A compound according to claim 1 wherein M¹, M², and M³ areselected from the group consisting of hydro (—H), halo (—F, —Cl, —Br,and —I), and C₁₋₄ alkyl.
 6. A compound according to claim 1 wherein Q isselected from the group consisting of oxy (—O—), and CZ¹Z² (where each Zis independently selected from the group consisting of hydro (—H) andC₁₋₄ alkyl, or one Z is the connecting bond to the pyridyl).
 7. Acompound according to claim 1 wherein R is selected from the groupconsisting of oxy (—O—), and CZ³Z⁴ (where each Z is independentlyselected from the group consisting of hydro (—H) and C₁₋₄ alkyl, or oneZ is the connecting bond to the pyridyl).
 8. A compound according toclaim 1 wherein A is amino (—NH—); E is aza (—N═); J¹, J², J³,and J⁴ arehydro (—H); M¹, M², and M³ are selected from the group consisting ofhydro (—H), halo (—F, —Cl, —Br, and —I), and C₁₋₄ alkyl; Q is selectedfrom the group consisting of oxy (—O—), and CZ¹Z² (where each Z isindependently selected from the group consisting of hydro (—H) and C₁₋₄alkyl, or one Z is the connecting bond to the pyridyl); and R isselected from the group consisting of oxy (—O—), and CZ³Z⁴ (where each Zis independently selected from the group consisting of hydro (—H) andC₁₋₄ alkyl, or one Z is the connecting bond to the pyridyl).
 9. Aprocess comprising applying a fungicidal amount of a compound accordingto claim 1 to a locus to control or prevent a fungal attack.
 10. Aprocess comprising applying a fungicidal amount of a compound accordingto claim 2 to a locus to control or prevent a fungal attack.
 11. Aprocess comprising applying a fungicidal amount of a compound accordingto claim 3 to a locus to control or prevent a fungal attack.
 12. Aprocess comprising applying a fungicidal amount of a compound accordingto claim 4 to a locus to control or prevent a fungal attack.
 13. Aprocess comprising applying a fungicidal amount of a compound accordingto claim 5 to a locus to control or prevent a fungal attack.
 14. Aprocess comprising applying a fungicidal amount of a compound accordingto claim 6 to a locus to control or prevent a fungal attack.
 15. Aprocess comprising applying a fungicidal amount of a compound accordingto claim 7 to a locus to control or prevent a fungal attack.
 16. Aprocess comprising applying a fungicidal amount of a compound accordingto claim 8 to a locus to control or prevent a fungal attack.